W. G. Stoil et al., in Helvetica Chemica Acta, Vol. 34 (1951), pp. 1937 to 1943, disclose N-[2-(dimethylamino)cyclohexyl]aniline and procedures for making it from N-(2-hydroxycyclohexyl)aniline and suggest that the compounds therein have antihistamine pharmacological properties, but nothing is said about the compounds of this invention or their use as antidepressant drugs.
J. W. Lewis et al., in an article entitled "The Reactions of Aromatic Nitroso-compounds with Enamines. Part I. The Reaction of Nitrosobenzene With 1-Morpholin-1-cyclohexene" in J. Chem. Soc. (London) (1972), Perkins Transactions I, Part III, pp. 2521-2524, discloses inter alia N-(2-morpholin-1-yl-cyclohexyl)phenylhydroxylamine and its hydrochloride salt, but it does not disclose or suggest the alkanoyl-anilide derivatives of this invention or their antidepressant properties.
J. W. Lewis et al., in an article entitled "Chemistry and Biological Activity of N-Substituted Hydroxylamines" in J. Pharmaceutical Sciences, December, 1974, Vol. 63, No. 12, pp. 1951-1953, discloses some N-Aryl-hydroxylamines such as N-[2-(N-pyrrolidinyl)cyclohexyl]-N-phenylhydroxylamine but these do not have useful CNS properties. Diuretic activity is alleged therein for the alcohols such as [2-(N-piperidinylcyclohexyl)(4-methoxyphenyl)methanol] and when the alcohol is acetylated, CNS depressant activity is said to appear. It also discloses the reaction of propionyl chloride with N-[2-(N-piperidinyl)-1,1-dimethylethyl]-N-phenylhydroxylamine to form the N-chloro compound which is then converted to a mixture of chlorinated aniline derivatives. That publication does not teach the compounds disclosed herein, how to make them, nor does it suggest the antidepressant properties which have been found for the compounds disclosed and claimed herein.
Szmuszkovicz U.S. Pat. No. 3,510,492 discloses and claims some 2-anilino- and 2-anilinomethylcycloalkylamines which are useful as antidiabetic drugs in that they can be administered in low dosages to reduce blood sugar. In column 3 this Szmuszkovicz patent discloses a Method B for preparing the N-(2-aminocycloalkyl)anilines of that invention and discloses the making and use of some N-(2-oxocycloalkyl)anilines (structure VI) compounds as chemical intermediates therein. Further, in column 3 thereof, that Szmuszkovicz patent discloses some N-(2-carboxycycloalkyl)anilines (structure XI) as chemical intermediates in the process for preparing Szmuszkovicz's cis-N-(2-aminocycloalkyl)anilines of that patent. In column 10 thereof, Szmuszkovicz discloses some 2-hydroxycycloalkylamines as chemical intermediates in disclosing how to prepare the starting materials for the compounds claimed therein. However, that patent does not disclose or suggest the compounds of this invention, how to prepare them or what pharmaceutical utilities they might have.
In my patent applications Ser. Nos. 746,191, filed Nov. 30, 1976, now abandoned and 777,759, filed Mar. 15, 1977, now abandoned I have disclosed and claimed the use of some N-(2-aminocyclopentyl)-N-alkanoxylanilides and their 2-N-oxides as antidepressant drugs. Those compounds are characterized by a cyclopentane-1,2-di-nitrogen structure, whereas the compounds of this invention are characterized by having an oxygen bonded to the cyclopentane ring carbon atom in the 2-position thereof.
Those in the pharmaceutical, chemical and pharmacological arts continue to need and look for active and more economical drugs which will have useful Central Nervous System (CNS) drug properties.